Bottom Line:
We found evidence of time-dependent rates in both coding and non-coding mitochondrial markers, in every group of animals that we studied.This indicates that, over long time frames, purifying selection gives way to mutational saturation as the main driver of time-dependent biases in rate estimates.The results of our study stress the importance of accounting for time-dependent biases in estimating mitochondrial rates regardless of the timescale over which they are inferred.

ABSTRACTEvolutionary timescales can be estimated from genetic data using the molecular clock, often calibrated by fossil or geological evidence. However, estimates of molecular rates in mitochondrial DNA appear to scale negatively with the age of the clock calibration. Although such a pattern has been observed in a limited range of data sets, it has not been studied on a large scale in metazoans. In addition, there is uncertainty over the temporal extent of the time-dependent pattern in rate estimates. Here we present a meta-analysis of 239 rate estimates from metazoans, representing a range of timescales and taxonomic groups. We found evidence of time-dependent rates in both coding and non-coding mitochondrial markers, in every group of animals that we studied. The negative relationship between the estimated rate and time persisted across a much wider range of calibration times than previously suggested. This indicates that, over long time frames, purifying selection gives way to mutational saturation as the main driver of time-dependent biases in rate estimates. The results of our study stress the importance of accounting for time-dependent biases in estimating mitochondrial rates regardless of the timescale over which they are inferred.

fig-1: Linear regressions of log-transformed rate estimates from mitochondrial markers in a range of metazoan taxa against the log-transformed calibration times that were used to estimate the rates.Separate analyses were performed for coding markers (A) and non-coding markers (B).

Mentions:
To test the relationship between mitochondrial rate estimates and calibration ages, we performed separate linear-regression analyses of coding and non-coding regions. All linear regressions were performed using log-transformed values of both estimated rates and calibration times. We found significant correlations between these two variables in coding markers (slope = −0.28, p = 1.58 × 10−12, R2 = 0.24) as well as non-coding markers (slope = −0.43, p = 1.38 × 10−12, R2 = 0.60) (Fig. 1 and Table S3).

fig-1: Linear regressions of log-transformed rate estimates from mitochondrial markers in a range of metazoan taxa against the log-transformed calibration times that were used to estimate the rates.Separate analyses were performed for coding markers (A) and non-coding markers (B).

Mentions:
To test the relationship between mitochondrial rate estimates and calibration ages, we performed separate linear-regression analyses of coding and non-coding regions. All linear regressions were performed using log-transformed values of both estimated rates and calibration times. We found significant correlations between these two variables in coding markers (slope = −0.28, p = 1.58 × 10−12, R2 = 0.24) as well as non-coding markers (slope = −0.43, p = 1.38 × 10−12, R2 = 0.60) (Fig. 1 and Table S3).

Bottom Line:
We found evidence of time-dependent rates in both coding and non-coding mitochondrial markers, in every group of animals that we studied.This indicates that, over long time frames, purifying selection gives way to mutational saturation as the main driver of time-dependent biases in rate estimates.The results of our study stress the importance of accounting for time-dependent biases in estimating mitochondrial rates regardless of the timescale over which they are inferred.

ABSTRACTEvolutionary timescales can be estimated from genetic data using the molecular clock, often calibrated by fossil or geological evidence. However, estimates of molecular rates in mitochondrial DNA appear to scale negatively with the age of the clock calibration. Although such a pattern has been observed in a limited range of data sets, it has not been studied on a large scale in metazoans. In addition, there is uncertainty over the temporal extent of the time-dependent pattern in rate estimates. Here we present a meta-analysis of 239 rate estimates from metazoans, representing a range of timescales and taxonomic groups. We found evidence of time-dependent rates in both coding and non-coding mitochondrial markers, in every group of animals that we studied. The negative relationship between the estimated rate and time persisted across a much wider range of calibration times than previously suggested. This indicates that, over long time frames, purifying selection gives way to mutational saturation as the main driver of time-dependent biases in rate estimates. The results of our study stress the importance of accounting for time-dependent biases in estimating mitochondrial rates regardless of the timescale over which they are inferred.